METHODS: A male infant who was admitted to Gansu Provincial Maternity and Child Health Care Hospital in May 2020 was selected as the study subject. Clinical data of the infant was collected. Genomic DNA was extracted from peripheral blood samples from the infant and his parents, and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.
RESULTS: The patient, a 4-day-old male infant, had presented with poor response, poor intake, feeding difficulties, and deceased at 8 months after birth. WES revealed that he has harbored a 0.643 Mb deletion in the 16p11.2 region, which encompassed key genes of the 16p11.2 microdeletion syndrome such as ALDOA, CORO1A, KIFF22, PRRT2 and TBX6. His father has carried the same deletion, but was phenotypically normal. The deletion was predicted to be pathogenic. The child was also found to harbor a maternally derived c.763C>T (p.R255X) hemizygous variant of the MECP2 gene, which was also predicted to be pathogenic (PVS1+PS4+PM2_Supporting).
CONCLUSIONS: The 16p11.2 deletion and the MECP2: c.763C>T (p.R255X) variant probably underlay the pathogenesis in this infant.
方法:以甘肃省妇幼保健院2020年5月收治的男婴为研究对象。收集婴儿的临床资料。从婴儿及其父母的外周血样本中提取基因组DNA,并进行全外显子组测序(WES)。通过Sanger测序验证候选变体。
结果:患者,一个4天大的男婴,反应不佳,摄入量差,喂养困难,并在出生后8个月死亡。WES透露,他在16p11.2区域有0.643Mb的缺失,其中包括16p11.2微缺失综合征的关键基因,如ALDOA,CORO1A,KIFF22、PRRT2和TBX6。他的父亲也进行了同样的删除,但表型正常。该缺失被预测为致病性的。还发现该孩子藏有母系衍生的c.763C>T(p。R255X)MECP2基因的半合子变体,这也被预测为致病性(PVS1+PS4+PM2_支持)。
结论:16p11.2缺失和MECP2:c.763C>T(p。R255X)变异可能是该婴儿发病机理的基础。